Prognostic factors in thyroid carcinomas: a 17-year outcome study

ABSTRACT Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Study on risk factors of recurrence in papillary thyroid microcarcinoma and papillary thyroid carcinomas with 1-2 cm diameter / 中华内分泌代谢杂志

Objective To explore risk factors of recurrence in papillary thyroid microcarcinomas ( PTMC ) and papillary thyroid carcinomas with 1-2 cm diameter. Methods From January, 2008 to December, 2010 in PLA General Hospital, 323 eligible patients received first surgery and diagnosed pathologically with papillary thyroid cancer≤2 cm were analyzed retrospectively. According to rumor size, patients were divided into PTMC and PTC of 1-2 cm, which were investigated recurrence factors. Results Finally we indentified 320 PTC≤2 cm, including 218 (68.1%)PTMCand102(31.9%)PTCof1-2cmwithamedianfollow-uptimeof72.5(55-90)months.32cases (10%)of patients relapse, includig 22 cases(10%)in PTMC and 10 cases(9. 8%)in PTC of 1-2 cm. In the clinical characteristics analyses of PTC≤2 cm, the PTC of 1-2 cm was different from PTMC in age, lymph node metastasis and TNM stage. The univariate analysis showed that tumor location and lymph node metastasis influenced recurrence of PTMC and PTC of 1-2 cm,while tumor foci and extrathytoidal extension were risk factors of recurrence in PTMC but not in PTC of 1-2 cm. Lymph node metastasis was independent factor which influenced the recurrence of PTMC and PT C of 1-2 cm according to COX multivariate analysis. Conclusion Disease recurrence did not differ significantly between the PTMC and PTC of 1-2 cm and lymph node metastasis was an independent recurrence factor.

Expression and significance of Slug in papillary thyroid carcinomas / 实用医学杂志

Objective To explore the clinical significance of Slug expression in papillary thyroid carci-noma(PTC). Methods Employed Ventana immunohistochemistry assay to determine the expression of Slug in 107 cases of PTC and para-tumorous normal tissue. The relationship with Slug expression in PTC and clinico-pathology data were also analyzed. Results Expression of Slug in PTC (65.4%, 70/107)and para-tumorous nor-mal tissue (14.0%,15/107)were statistically different (P < 0.001). Overexpression of Slug in PTC was signifi-cantly associated with capsular invasion and lymph node metastasis (P < 0.05). Conclusion Overexpression of Slug in PTC is associated with capsular invasion and lymph node metastasis , these may suggest some clinical significance of Slug expression in PTC in predicting lymph node metastasis and prognosis.

"A cooperative achievement of, and shared by, four academic societies——At the moment of the publication of ""Guidelines on the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Carcinomas""" / 中华内分泌代谢杂志

Guidelines on the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Carcinomas is written by Chinese Society of Endocrinology,Chinese Society of General Surgery Endocrinology Group,China Anti-Cancer Association Head and Neck Tumor Professional Committee,and Chinese Society of Nuclear Medicine.The guideline has systematically established a series of standards related to thyroid nodules.It reflects the scientific spirit of multidisciplinary cooperation and mutual understanding.

Implication of integrin β4 expression in thyroid follicular cancer metastasis / 中华内分泌代谢杂志

Objective To investigate the effect of integrin β4 expression on the metastasis potential of human thyroid follicular cancer cells. Methods Metastasis potential was observed and grouped in human thyroid follicular cancer cell line, CGTHW-1 cells, depending on the cells' penetrating ability in artificial matrigel. The expression of integrin β4 mRNA and protein were determined by immunocytochemistry, Western blot, and semiquantitative RT-PCR. Results The mRNA and protein expressions of integrin β4 were significantly higher in cells with high metastasis potential [0.277 5 ±0.034 0 vs 0. 187 5 ±0.022 2 ( Immunohistochemistry ), 0. 099 7 ± 0.0185 vs 0.039 0±0.010 2(Western blot), 0.555 0±0. 101 2 vs 0.270 0±0.029 9(RT-PCR), all P＜0.01]. Conclusion Integrin β4 may play an important role in human thyroid cancer invasion. It seems probably to be a potential target for human thyroid cancer treatment.

The Analysis of Tumor Aggressiveness accord- ing to Tumor Size in Occult Papillary Thyroid Carcinoma

PURPOSE: Occult papillary thyroid carcinomas (OPC) are defined as tumors measuring 0.5 cm. A near-total or total thyroidectomy with a central lymph node dissection is the preferred treatment. The early detection and treatment of OPC might be warranted through the routine use of thyroid USG and USG-guided FNA.

Methylation of TSHR Gene Promoter in Papillary Thyroid Carcinoma / 医学研究杂志

Objective To investigate the relationship between the characteristics of promoter methylation of thyroid stimulating hormone receptor(TSHR) gene in papillary thyroid Carcinomas(PTC) and the clinical manifestation of PTC. Methods The methylation status of TSHR gene was detected by methylation specific PCR technique(MSP).Results (1) The methylation rate of TSHR gene in PTC tissues was 64.7%(22/34),while the methylation rate of TSHR gene in adjacent thyroid tissues(ATT) was 26.5%(9/34),and the rate of methylation of TSHR promoter in PTC was significantly higher than of ATT(P

Clinical Features of Well Differentiated Thyroid Carcinomas in Pregnant Women / 대한내분비학회지

BACKGROUND: In differentiated thyroid carcinomas (DTC), it has been reported that pregnancy may accelerate the course of the disease. But recent evidences suggested that the prognosis of DTC during pregnancy was similar to that of DTC in non-pregnant women of the same age. Also the optimal timing for the treatment is still controversial. We evaluated the clinical features of DTC in pregnant women. METHOD: We reviewed the histories of patients in whom the DTC was diagnosed before or during the pregnancy between 1994 and 1999. DTC were diagnosed by fine needle aspiration and the patients were treated by thyroid surgery. RESULTS: Six women who had a mean age of 30 years (27-34 years) were identified. The mean follow-up duration was 41 months (13-70 months). All patients had noticed a lump in their necks. In three patients, the nodules increased in size during pregnancy. A fine needle aspiration revealed a suspected malignancy in five patients and a postoperative biopsy confirmed the malignancy in one patient who had a preoperative cytologic diagnosis of nodular hyperplasia. All tumors were well differentiated and ranged in size from 1 to 6.5 cm. Radioactive iodine ablation and thyroid hormone suppression treatment were administered in five patients except in one case of papillary microcarcinoma. One patient had residual tumors in the right cervical lymph nodes and both lungs. She underwent repeated surgery and radioactive iodine therapy. CONCLUSION: This reports suggest that the DTC which is associated with pregnancy may have a similar prognosis to that of non-pregnant women and that the treatment of DTC in pregnant women may be safely delayed until after delivery in most patients. The treatment should not be delayed for more than a year.

Expressions of five matrix metalloproteinase genes in papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective To study the expressions of matrix metalloproteinase (MMP) gene family in papillary thyroid carcinoma (PTC) and its relationship to the pathogenesis of PTC. Methods The thyroid tissues of patients were collected in surgical operation, including 8 cases with papillary thyroid carcinoma, 7 cases with Hashimoto′s thyroiditis, 8 cases with adenoma and 8 normal tissues. The total RNA of these samples were extracted and purified by the method of acidic phenol. The gene expressions of MMP-2, MMP-9, MMP-14, MMP-25 and MMP-26 were assayed by RT-PCR and 1% agarose gel electrophoresis. The fluorescent degree of electrophoretic bands was detected by automatic gel scanner and analyzed statistically in order to compare the levels of gene expressions among 4 groups. Results The positive rates and the levels of MMP-2, MMP-9 and MMP-14 gene expressions in PTC group were significantly higher than those in other 3 groups (all P

The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence / 대한내분비학회지

BACKGROUND: Thyroglobulin (Tg) measurement is primarily used to monitor patients with well differentiated thyroid carcinomas (WDTC) for tumor recurrence. We evaluated the correlations between fold responses of thyroglobulin levels and TNM stages (and MACIS scores) at recurrent group. Also correlations between preoperative Tg levels and Tg (on or off replacement) levels at the time of recurrence were evaluated. Postoperative Tg levels between recurrent and non-recurrent groups were analyzed for the use of assessing risk of recurrence. METHODS: One hundred twenty five cases of WDTC who had total thyroidectomy and (131)I remnant thyroid ablation were finally included in this study. After optimal TSH stimulations (>30 microIU/mL), (131)I whole body scan (WBS) was performed. We interpreted as a recurrence only when abnormal findings on the (131)I WBS were detected. Preoperative, immediate postoperative and follow-up Tg tlevels were regularly measured. RESULTS: Difference of preoperative Tg levels between recurrent and non-recurrent groups was not significant (27.5+/-4.2 ng/mL vs. 16.0+/-10.9 ng/mL). Also differences of immediate postoperative Tg (on or off replacement) levels between two groups was not significant (2.4+/-3.8 ng/mL vs. 3.6+/-3.l ng/mL, 33.4+/-4.8 ng/ml vs. 24.5+/-4.8 ng/mL, respectively). Tg levels on replacement at 24 months after surgery between recurrent and non-recurrent groups were significantly different (2.2+/-4.8 ng/mL, 15.9+/-6.5 ng/mL, p<0.001) and also Tg levels off replacement between recurrent and non-recurrent groups were significantly different (4.0+/-6.6ng/mL vs. 49.4+/-9.3 ng/mL, p<0.001). Fold responses between recurrent and non-recurrent groups were significantly different (2.0+/-3.1 ng/mL, 5.0+/-4.1 ng/mL, p=0.009). Fold responses between recurrent and non- recurrent groups were significantly different according to TNM stages (p=0.002) but not different according to MACIS scores. Preoperative Tg levels were correlated Tg (on or off replacement) levels at the time of recurrence (p=0.02, r=0.4: p<0.001, r=0.6, respectively). Sensitivity, specificity, accuracy of Tg levels over 2 ng/mL on replacement were 95%, 73%, 84% but those of Tg levels over 7 ng/mL off replacement were 83%, 70%, 77%. CONCLUSION: Fold responses may predict prognosis of WDTC. Small postoperative increase in serum Tg levels may indicate a large increase of tumor mass in cases of normal or low preoperative Tg levels. Tg levels over 2 ng/mL on replacement or 7 ng/mL off replacement during follow-up may suggest the recurrence of WDTC.

Expression of p53 and MDM2 Proteins in Thyroid Carcinomas

The nuclear protein p53 is a tumor suppressor gene product that functions in pathways of cell cycle control and in the repair of damaged DNA. The MDM2 gene codes for a cellular protein that can complex the p53 gene product and negatively regulate its function. Interestingly an autoregulatory feedback loop is set up to regulate the activity of p53 protein and MDM2 gene expression. To evaluate the role of p53 and MDM2 proteins in thyroid carcinogenesis, the author tried immunohistochemical studies in the paraffin embedded sections of 58 thyroid carcinoma cases, including 30 papillary carcinomas, 20 follicular carcinomas, and 8 undifferentiated carcinomas. p53 protein expression was found in 8 cases (26.7%) of papillary carcinomas. It was found in all the cases of undifferentiated carcinomas and not found in the follicular carcinomas. The staining intensity and the frequency scores were more prominent in undifferentiated carcinomas. MDM2 protein expression was found in only 6 cases of papillary carcinomas. It was not expressed in follicular carcinomas or undifferentiated carcinomas. The staining intensity is less than moderate and the frequency score was usually focal. In papillary carcinomas, the correlation of p53 and MDM2 expression was insignificant. In conclusion, p53 may play a major role in tumorigenesis or the progression of undifferentiated carcinomas, but not in the other carcinomas. As compared with papillary carcinomas, follicular carcinomas are regarded as taking a different carcinogenetic pathway. The overexpression of p53 and MDM2 proteins in papillary carcinomas is presumed not to be necessarily correlated with the p53-MDM2 complex formation.